Exploring prior diseases associated with incident late-onset Alzheimer’s disease dementia

Studies have identified prior conditions associated with late-onset Alzheimer’s disease dementia (LOAD), but all prior diseases have rarely been screened simultaneously in the literature. Our objective in the present study was to identify prior conditions associated with LOAD and construct pathways for them. We conducted a population-based matched case-control study based on data collected in the National Health Insurance Research database of Taiwan and the Catastrophic Illness Certificate database for the years 1997–2013. Prior diseases definitions were based on the first three digits of the codes listed in the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). Inclusion criteria required that each ICD-code existed for at least 1 year and incurred at least 2 outpatient visits or inpatient diagnosis. The case group comprised 4,600 patients newly diagnosed with LOAD in 2007–2013. The LOAD patients were matched by sex and age to obtain 4,600 controls. Using stepwise multivariate logistic regression analysis, diseases were screened for 1, 2 …, 9 years prior to the first diagnosis of LOAD. Path analysis was used to construct pathways between prior diseases and LOAD. Our results revealed that the following conditions were positively associated with the incidence of LOAD: anxiety (ICD-code 300), functional digestive disorder (ICD code 564), psychopathology-specific symptoms (ICD-code 307), disorders of the vestibular system (ICD-code 386), concussion (ICD-code 850), disorders of the urethra and urinary tract (ICD-code 599), disorders of refraction and accommodation (ICD-code 367), and hearing loss (ICD-code 389). A number of the prior diseases have previously been described in the literature in a manner identical to that in the present study. Our study supports the assertion that mental, hearing, vestibular system, and functional digestive disorders may play an important role in the pathogenesis of LOAD.

现有研究已明确与晚发性阿尔茨海默病痴呆（Late-onset Alzheimer’s disease dementia，LOAD）相关的既往共病，但现有文献中鲜有同时筛查所有既往疾病的报道。本研究旨在明确与晚发性阿尔茨海默病痴呆相关的既往共病，并构建其关联通路。我们基于1997-2013年中国台湾地区全民健康保险研究数据库（National Health Insurance Research Database）与重症伤病证明数据库中的数据，开展了一项人群匹配病例对照研究。既往疾病的判定标准基于《国际疾病分类第9版临床修订版（International Classification of Diseases, Ninth Revision, Clinical Modification，ICD-9-CM）》所列编码的前三位数字。纳入标准要求，相关国际疾病分类编码对应的疾病需持续存在至少1年，且至少有2次门诊就诊记录或1次住院诊断记录。病例组纳入2007-2013年新确诊的4600例晚发性阿尔茨海默病痴呆患者，按照性别与年龄进行1:1匹配，获得4600例对照个体。本研究采用逐步多因素logistic回归分析，对晚发性阿尔茨海默病痴呆首次确诊前1至9年的既往疾病进行筛查；同时通过路径分析构建既往疾病与晚发性阿尔茨海默病痴呆之间的关联通路。研究结果显示，以下疾病与晚发性阿尔茨海默病痴呆的发病呈正相关：焦虑症（ICD编码300）、功能性消化紊乱（ICD编码564）、特异性精神病理症状（ICD编码307）、前庭系统紊乱（ICD编码386）、脑震荡（ICD编码850）、尿道与尿路紊乱（ICD编码599）、屈光与调节障碍（ICD编码367）以及听力损失（ICD编码389）。本研究识别的部分既往疾病，已在现有文献中以与本研究一致的方式被报道。本研究证实，精神系统、听力、前庭系统及功能性消化紊乱可能在晚发性阿尔茨海默病痴呆的发病机制中发挥重要作用。